Xiaofeng Zheng, Ph.D.
RNA and protein function
Professor, College of Life Sciences, Peking University
tel：
Postcode：010-6276-5913
E-mail：xiaofengz@pku.edu.cn
1. The regulatory functions of protein modifications in the pathways of NF-κB、p53 and DNA damage response
2. Identification of novel proteins that play important roles in inflammation and tumorigenesis
3. The functions of exosomal proteins in tumor metastasis
Our research is mainly focused on the functional study of human disease related proteins. We take molecular, biochemical, cellular biology approaches to investigate the biological roles and molecular mechanisms of HSCARG and hCINAP in inflammation and tumorigenesis. Besides, we identified some novel regulators and substrates of ubiquitination and NEDDylation in the pathways of p53, NF-κB and DNA damage response, and studied their regulatory mechanism. We demonstrated that HSCARG and hCINAP play important roles in regulating the activities of NF-κB and p53 by modulating the ubiquitination or NEDDylation of the key proteins in these pathways. HSCARG could negatively regulate the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting deubiquitinase OTUB1. In the DNA damage response, we found that HSCARG is a novel regulator of H2A ubiquitination by downregulating PRC1 ubiquitin E3 ligase activity, unraveling a novel mechanism for the regulation of H2A ubiquitination and elucidates how regulators of H2A ubiquitination affect cell cycle. Studying of the function of hCINAP revealed that this protein is a critical regulator of 18S rRNA and demonstrated its important role in tumorigenesis and metastasis through modulating the Warburg effect. In addition, we also interested in identification of exosomal proteins that are critical for tumor metastasis.
Liao LM, Yang P, Zhang WL, Yu SY, Jing HM, Zheng XF. (2024) CD98hc promotes drug resistance in extranodal natural killer/T cell lymphoma through tumor cell-derived small extracellular vesicles. Sci. Signal., 17: eadf9388.
Zhang J, Chen YT, Gong X, Yang YF, Gu Y, Huang L, Fu JF, Zhao ML, Huang YH, Li LL, Liu WZ, Wan YJ, He XL, Ma ZF, Zhao WY, Zhang M, Tang T, Wang YZ, Thiery JP, Zheng XF, Chen LM. (2024) GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in patients with breast cancer. J. Biol. Chem., 300: 107780.
Fu JF, Zhou SR, Xu HL, Liao LM, Shen H, Du P, Zheng XF. (2023) ATM-ESCO2-SMC3 axis promotes 53BP1 recruitment in response to DNA damage and safeguards genome integrity by stabilizing cohesin complex. Nucl. Acids Res., 51: 7376-7391.
Wei M, Huang XP, Liao LM, Tian YL, Zheng XF. (2023) SENP1 decreases RNF168 phase separation to promote DNA damage repair and drug resistance in colon cancer. Cancer Res., 83: 2908-2923.
Zhuge RP, Huang XP, Zheng XF. (2023) Insight into the multi-faceted roles of the structure and function of an atypical adenylate kinase AK6/hCINAP. Prog. Biochem. Biophys., 50: 1122- 1132.
Huang XP, Zhao Y, Wei M, Zhuge RP, Zheng XF. (2023) hCINAP alleviates senescence by regulating MDM2 via p14ARF and the HDAC1/CoREST complex. J. Mol. Cell Biol., 15: mjad015.
Zhuge RQ, Wang C, Wang J, Yu SY, Liao LM, Zheng XF. (2023) hCINAP controls lineage differentiation of embryonic stem cells by regulating NEDD4 liquid-liquid phase separation-mediated YAP1 activation. Cell Rep., 42: 111935.
Liao LM, Xu HL, Zhao YH, Zheng XF. (2023) Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies. Front. Med., 17: 805-822.
Zhao Y, Huang XP, Zhu D, Wei M, Luo JC, Yu SY, Tian YL, Zheng XF. (2022) Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy. Cell Death Differ., 29: 2531-2544.
Huang XP, Yang YF, Zhu D, Zhao Y, Wei M, Li K, Zhu HH, Zheng XF. (2022) PRMT5-mediated RNF4 methylation promotes therapeutic resistance of APL cells to As2O3by stabilizing oncoprotein PML-RAR alpha. Cell. Mol. Life Sci., 79: 319.
Yu SY, Zang WC, Qiu YC, Liao LM, Zheng XF. (2022) Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis. Oncogene, 41: 46-56.
Zhu D, Xu RD, Huang XP, Tang ZF, Tian YL, Zhang JF, Zheng XF. (2021) Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1.Cell. Death. Differ., 28: 1773-1789.
Xu RD, Yang YF, Zheng XF. (2021) Unique structural features of the adenylate kinase hCINAP/AK6 and its multifaceted functions in carcinogenesis and tumor progression. FEBS Lett., 595: 2071-2084.
Chen SW, Wang YB, Liao LM, Meng L, Li JJ, Shi C, Han H,Zheng XF, Shen H. (2020) Similar repair effects of human placenta, bone marrow mesenchymal stem cells and their exosomes for damaged SVOG ovarian granulosa cells. Stem. Cell. Int., 8861557.
Yang YF, Yang CZ, Li TT, Yu SY, Gan TT, Hu JZ, Cui J, Zheng XF. (2020) The deubiquitinase usp38 promotes nhej repair through regulation of HDAC1 activity and regulates cancer cell response to genotoxic insults. Cancer Res., 80: 719-731.
Zang WC, Zheng XF. (2020) Structure and functions of cellular redox sensor HSCARG/NMRAL1, a linkage among redox status, innate immunity, DNA damage response, and cancer.Free Radic Biol Med., 160: 768-774.
Chen SW, Wang YB, Liao LM, Meng L, Li JJ, Shi C, Han H, Zheng XF, Shen H. (2020) Similar repair effects of human placenta, bone marrow mesenchymal stem cells and their exosomes for damaged SVOG ovarian granulosa cells. Stem. Cell. Int., 8861557.
Min Wei, Jie Wang, Jianfeng Fu, Chao Wang, Siru Zhou, Yulin Li, Huilin Xu, Yuhan Zhao, Yuxin Shi
